Physiologically and non-physiologically generated reactive oxygen intermediates damage cell elements such as DNA, protein and lipids, and may be responsible for degenerative diseases, such as cancer, and the aging process. The goal of this proposal is to understand how cells prevent the potential damage by reactive oxygen. Genes that control the responses to reactive oxygen (oxidative stress) have been isolated recently. One system, the superoxide response genes (soxRS gene), has drawn a special attention since soxRS can be activated not only by superoxide, but also by nitric oxide. The soxRS genes encode two proteins, SoxR and SoxS. SoxR is considered as a redox sensor, and controls the expression of the soxS gene whose product SoxS then stimulates expression of a group of genes that encode defense functions. Recent evidence indicates that SoxR contains a [2Fe2S] cluster that is required for SoxR to 2Fe2S] cluster in SoxR, and exploring its assembly and disassembly processes.